Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation

Abstract

Summary The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of Tregs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs.

Homeostatic Control of Sebaceous Glands by Innate Lymphoid Cells Regulates Commensal Bacteria Equilibrium

“…These studies, together with the reliance of ILCs on hair follicles reported herein, suggest that hair follicles are central to tissue-immune crosstalk in skin, but this is not unidirectional; hair follicles in turn rely on monocytes for quorum sensing-mediated regeneration (Chen et al, 2015), on regulatory T cells for stem cell maintenance (Ali et al, 2017), and, as demonstrated in this study, on ILCs for sebaceous gland control.…”

Skin and Its Regenerative Powers: An Alliance between Stem Cells and Their Niche

“…Albeit outside the scope of this review, they have all been found to impact skin homeostasis (Ali et al, 2017; Chang et al, 2013; Driskell et al, 2013; Festa et al, 2011; Plikus et al, 2008; Rabbani et al, 2011). How they contribute to wound healing, whether through direct contribution to re-epithelialization or through interactions with epithelial stem cells, is an exciting topic for future study.…”

Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease

“…In skin, resident T regs are found near the stem cell niche of hair follicles (Ali et al, 2017) (Figure 3C). Rosenblum and colleagues recently reported that T reg numbers fluctuate during the normal hair cycle, peaking in telogen when stem cells are quiescent, and then reaching a low during anagen (Ali et al, 2017).…”

“…Similar to macrophage depletion, T reg deficiency also derails new hair growth stimulated by hair depilation (Ali et al, 2017). It is presently still unclear whether depilation elicits a injury response by immune cells.…”

“…A number of immune-derived cytokines and growth factors such as amphiregulin, IL-6 and IL-22 are known to directly promote healing (Ali et al, 2017; Keyes et al, 2016; Lindemans et al, 2015). Infusing damaged tissues with recombinant versions of these factors and/or identifying agonists for their downstream targets in stem cells could greatly enhance repair.…”